Solution Structure of the Second PDZ Domain of the Neuronal Adaptor X11α and its Interaction with the C-terminal Peptide of the Human Copper Chaperone for Superoxide Dismutase

• Published in: Journal of biomolecular NMR 2005-07, Vol.32 (3), p.209-218
• Main Authors: Duquesne, Aude E., Ruijter, Martina de, Brouwer, Jaap, Drijfhout, Jan W., Nabuurs, Sander B., Spronk, Chris A. E. M., Vuister, Geerten W., Ubbink, Marcellus, Canters, Gerard W.
• Format: Article
• Language: English
• ISSN: 0925-2738; 1573-5001
• DOI: 10.1007/s10858-005-7333-1

Protection against reactive oxygen species is provided by the copper containing enzyme superoxide dismutase 1 (SOD1). The copper chaperone CCS is responsible for copper insertion into apo-SOD1. This role is impaired by an interaction between the second PDZ domain (PDZ2 alpha ) of the neuronal adaptor protein X11 alpha and the third domain of CCS (McLoughlin et al. (2001) J. Biol. Chem., 276, 9303-9307). The solution structure of the PDZ2 alpha domain has been determined and the interaction with peptides derived from CCS has been explored. PDZ2 alpha binds to the last four amino acids of the CCS protein (PAHL) with a dissociation constant of 91 plus or minus 2 mu M. Peptide variants have been used to map the interaction areas on PDZ2 alpha for each amino acid, showing an important role for the C-terminal leucine, in line with canonical PDZ-peptide interactions.